Synopsis: This study details findings from two separate trials, both sponsored by GlaxoSmithKline. One trial involved 847 patients who were seronegative for herpes simplex virus (HSV) types 1 and 2, and the other trial included 2,491 subjects, 1,867 of whom were seronegative for HSV-2. All of the study subjects had partners with HSV-2 infection.

Subjects were randomized to immunization at zero, one, and six months with an HSV-2 glycoprotein-D–subunit vaccine (not yet commercially available) or placebo. HSV-2 infection was established by educating patients about the appearance of lesions, and having patients visit the office for culture and/or polymerase chain reaction. Details of the randomization, masking, or allocation concealment were not given. Analysis was appropriately done by intention-to-treat, so the results include the approximately 10 percent of patients who failed to complete the vaccine series. The primary outcome was vaccine efficacy, measured as the reduction in the attack rate between immunized and nonimmunized patients. Subjects were followed for a mean of 19 months.

The researchers found that although the vaccine did not reduce the overall attack rate, it did reduce the rate in women, particularly those who were seronegative for both HSV-1 and HSV-2 at study entry (absolute risk reduction [ARR]: 9 percent; number needed to treat [NNT]: 11). The vaccine did not prevent infection (symptomatic disease and/or seroconversion). While the authors note a nonsignificant trend favoring women, they fail to mention a trend toward harm in men. This seems like “data dredging” (i.e., sorting through the data to find a subgroup in whom the intervention works). However, the authors claim that they changed the primary outcome to efficacy in women before looking at the data for the second group of subjects.

The cost issues must be considered. Because the vaccine only works in women who are HSV-1– and HSV-2–negative, should we spend the money needed to screen for both HSV types to detect the minority of patients who could benefit from the vaccine? If so, more than 100 patients would need to be screened to prevent one disease occurrence, which may not be cost effective.

Bottom Line: A new HSV-2 vaccine is safe and reduces the attack rate in women who are both HSV-1– and HSV-2–negative (ARR: 9 percent; NNT: 11) and who are in a relationship with someone who has HSV-2 infection. The decision to use the vaccine should be based on a guideline that considers this information as well as other data on cost, benefit, and harm. (Level of Evidence: 1b)